I-CAR T-Cell yokwelapha umdlavuza wamaphaphu ongewona omncane

Mashi 2024 : I-CAR T-cell therapy iyindlela yokwelapha umdlavuza engaba khona, ikakhulukazi ezinkingeni ze-hematological. Kodwa-ke, ukusebenza kahle kwayo kumathumba aqinile, njengomdlavuza wamaphaphu, kulinganiselwe ngenxa yemvelo ye-tumor microenvironment's immunosuppressive. Abacwaningi bakha amaseli esizukulwane esilandelayo e-CAR T ukuze athuthukise ukungena kwawo, ukusinda, nokuphikelela ngaphakathi kwezifo ezibulalayo. Izivivinyo zemitholampilo ziyaqhubeka ukuhlola ukuphepha nokusebenza kokwelashwa kwe-CAR T-cell kumdlavuza wamaphaphu, ngemiphumela ethile ethembisayo. Ukuphunyuka kwe-antigen, izithiyo zokugonywa kwamasosha omzimba, kanye nokulimala kwesimila okuqondiswe kuso kuphakathi kwezinselelo ekwelapheni kwamaseli e-CAR T omdlavuza wamaphaphu. I-Engineering CAR iyakha, ishintsha isisu imvelo encane, nokusebenzisa amaseli e-CAR T angekho eshalofini amanye amasu okubhekana nalezi zinkinga.

Esinye sezibhedlela ezihamba phambili e-China senze ngempumelelo ukuhlolwa kwe-CAR T-Cell therapy ku umdlavuza wamaphaphu weselula ongewona omncane iziguli. I-CAR T-Cell kuyo yonke le midlavuza iyasebenza ezigulini ngemuva kwemigudu ethile yokwelashwa efana nokuhlinzwa, ichemotherapy kanye neradiotherapy kodwa zabuyela emuva.

Kuzo zonke izifo ezibulalayo, umdlavuza wamaphaphu unezinga eliphezulu lokufa kwabantu emhlabeni wonke. Izinhlobonhlobo ezikhulayo zemithi ye-immunotherapeutic, ikakhulukazi leyo eqondise amasosha omzimba e-monoclonal, isetshenziswe ekwelapheni isifo esibulalayo esikhathini samanje. immunotherapy isikhathi, nakuba isenezihibe eziningi. Ngaphezu kokusetshenziswa ngempumelelo ngokumelene nomdlavuza we-hematological, amaseli e-T (CAR-T) e-chimeric antigen receptor-modified aphinde adala amathuba amasha okwelashwa kokuzivikela komzimba kwamathumba aqinile, njengomdlavuza wamaphaphu. Ukushoda kwama-antigen aqondene nesimila afanelekile, i-immune immunosuppressive tumor microenvironment, izinga eliphansi lokungena kweseli le-CAR-T kuzicubu zesimila, kanye nemiphumela engeyona eqondisiwe, njll. kwenza kube nzima ukukhomba. umdlavuza wamaphaphu-ama-antigens athile anamaseli e-CAR-T ashintshiwe. Phakathi naleso sikhathi, ngenxa yobunzima obuningi njenge-tumor lysis syndrome, i-neurotoxicity syndrome, kanye i-cytokine release syndrome, ukusetshenziswa komtholampilo kwamaseli e-CAR-T kusakhawulelwe. Ngenhloso yokuhlinzeka ngemibono emisha nezindlela zezifundo zangaphambi komtholampilo kanye nezivivinyo zomtholampilo ze-CAR-T cell therapy yomdlavuza wamaphaphu, sibeka isakhiwo esiyisisekelo nezici zesizukulwane samaseli e-CAR-T kulokhu kubuyekezwa, sifingqa isizinda esijwayelekile esihambisana nesimila. ama-antigen, futhi ugqamise izinselele zamanje.

Ukwakheka kwe-CARS

Kusukela ekuqaleni kwayo, ukusetshenziswa kwama-CAR ekwelapheni kwe-T-cell kuye kwadlula ezizukulwaneni ezine eziphindaphindayo, zonke ezisekelwe ezizindeni zesignali ye-CAR ye-intracellular. Isizukulwane sokuqala sama-CAR sasinomsebenzi obuthakathaka kanye nesikhathi esifushane sokusinda se-vivo ngoba aqukethe kuphela isignali yokuqaphela i-antigen. Indawo yokudlulisa isignali yesizukulwane sesibili nesesithathu se-CAR, ngokulandelana, iqukethe i-molecule eyodwa nambili ye-costimulatory. Lezi zinguquko zenziwe ukuze kwandiswe ukusinda kwama-T cell, i-cytotoxicity, nokwanda. Ama-molecule e-co-stimulatory kuma-CAR athuthukisiwe, okwenza ngcono ukusebenza kwamaseli e-CAR-T. I-4-1BB noma i-CD28 yizizinda ezimbili ezikhuthazayo zesizukulwane sesibili ezisetshenziswa kakhulu. Ukwengeza, i-cytotoxicity, ukukhiqizwa kwe-cytokine, nokusebenza kwe-T cell konke kuboniswe ukuthi kuthuthukiswe yi-DNAX-activating protein 10 (DAP10). Ngokusekelwe emigqeni yamaseli omdlavuza wamaphaphu okungewona omncane (NSCLC), ukubambezeleka kokuqala komdlavuza wamaphaphu kanye nokwanda komsebenzi wokulwa nesimila kuboniswe kumamodeli wezilwane we-vivo we-xenotransplantation yomdlavuza wamaphaphu. Ama-cytokines ane-pro-inflammatory kanye nama-co-stimulating ligands angeziwe ekwakhiweni kwesizukulwane sesine se-CAR-T ukuze kusizwe ama-T-cells ukuthi angene futhi adlulele ngale kwezindawo zokucindezela ze-TME ezinonya.

Ukukhulisa kanye nokusebenza kahle kwe-anti-tumor kwamaseli e-CAR-T kuye kwaboniswa ukuthi kuthuthukiswe ngokuthuthukisa isakhiwo semojula ye-extracellular ngaphezu kwamamojula okudlulisa isignali ye-intracellular. Ngokuka-Qin et al., i-single-chain variable fragment (scFv), ebophezela futhi ikhuthaze ukunwetshwa, ukufuduka, nokuhlasela kweqoqo lamaseli okuhlukanisa 4 (CD4)+ CAR-T, wenziwe waguquguquka ngokwengeziwe ngokungezwa yesakhiwo sehinge. Yize amaseli esizukulwane sesibili e-CAR-T eqhubeka nokuba indlela ejwayelekile yokusetshenziswa kokwelapha, ukwakheka kwesakhiwo sama-CARs kuthuthukiswa njalo futhi kubalulekile ekusebenzeni kahle kwe-CAR. I-T

Ukwelashwa kwe-CAR T-Cell kumdlavuza wamaphaphu kanye ne-antigen eqondiwe

Lapho i-target-antigen ivezwa ngokukhethekile kumaseli omdlavuza noma igcizelelwe ngokweqile kuwo wonke noma iningi lamaseli omdlavuza wamaphaphu uma kuqhathaniswa namaseli avamile, lokhu kuyinkomba engcono kakhulu yokwelashwa kweseli ye-CAR-T. Yize inani elikhulu lama-antigens ahlobene ne-tumor (TAA) atholwe kumdlavuza wamaphaphu ongewona amancane (ama-NSCLC), ambalwa kuphela alawa ma-antigen aqondiswe ngqo amaseli e-CAR-T (8). Ukwengeza, amanye alawa ma-antigen ahlosiwe nawo avezwa ngokubuthakathaka ezicutshini ezinempilo, okunikeza amanye amaseli e-CAR-T amandla okuhlasela amaseli anempilo.

I-Epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), mesothelin (MSLN), prostate stem cell antigen (PSCA), mucin 1 (MUC1), carcinoembryonic antigen (CEA), tyrosine kinase-like orphan receptor ( I-ROR1), i-death ligand 1 (PD-L1) ehleliwe, kanye ne-CD80/CD86 ziphakathi kwezinto okuhlosiwe okwamanje ezifundelwa i-CAR.

Isiguli somdlavuza wamaphaphu sithola ukwelashwa kwe-CAR T-Cell

NgoNovemba ka-2009, isiguli sathola isisindo samaphaphu sangakwesokunxele saphinde sahlinzwa kakhulu umdlavuza wamaphaphu. I-pathology: i-lung adenocarcinoma;
Kusukela ngo-Jan 2013 kuya ku-Jan 2017, ama-metastases amathathu obuchopho enzeka, futhi ukuhlinzwa nokwelashwa ngemisebe kwanikezwa ngokulandelana ngokulawulwa okungalungile;
Kusukela ngoMashi 2017 kuya kuSepthemba 2017, kuma-metastases obuchopho, amaseli e-mesoCAR-αPD1 aveza i-PD-1 antibody anikezwa izifundo zokwelashwa eziyisithupha. Ngemuva kokwelashwa, i-PR yahlolwa futhi izicubu zancipha kakhulu ngenani elincane kuphela lezinsalela.

Ukwelashwa kwe-CAR T-Cell eChina

I-CAR-T Cell therapy e-China ikhula ngesivinini esikhulu. Imiphumela ye Ukwelashwa kwe-CAR T-cell eChina futhi izinga lokwelapha lilonke liphakathi kwezingcono kakhulu emhlabeni njengamanje. Kukhona izinhlolo zomtholampilo ezingaphezu kuka-300 ezenzekayo China yokwelashwa kwamaseli e-CAR T. I-China iphakathi kwamazwe okuqala ukunikeza ukwelashwa kwe-CAR T Cell ngemva kwalokho USA & UK. Ngokwenombolo yokuhlolwa komtholampilo kwe-CAR-T, i-China ingeyesibili ngemuva kwe-USA, ibhalise cishe u-33% wezivivinyo emhlabeni wonke. Inani lezokwelapha ze-CAR T-cell ekuthuthukisweni komtholampilo liye lenyuka kakhulu eminyakeni yamuva. Njengamanje, e-China, kunezinhlolo zomtholampilo eziqhubekayo ezingaphezu kuka-300 ezinkingeni ze-hematological kanye nezimila eziqinile.

Ukuhlola okubanzi kweShayina kanye nempumelelo ekusesheni ama-antigen anoveli ahlosiwe, ukwenziwa ngcono kwesakhiwo se-CAR, i-cocktail CAR-T therapy, ukwelapha okuhlangene, kanye nokwandiswa kwezicelo zamaseli e-CAR-T, kusho ukuthi okwamanje sisonqenqemeni lwenguquko e-CAR- Ukwelashwa kwe-T. I-US FDA igunyazile Ukwelashwa kwe-CAR T Cell ngokuphindela emuva kwe-B Acute lymphoblastic leukemia, i-lymphoma & ne-myeloma eminingi. China isanda kugunyaza ukwelashwa kwe-CAR T-Cell kweminye imidlavuza eqinile. Iziguli ezivela emhlabeni wonke kungenzeka zizuze kulokhu kuthuthukiswa.

Ungahle uthande ukufunda: Ukwelashwa kwe-CAR T-Cell eChina

Kuyini ukwelashwa kwe-CAR T-Cell (Chimeric antigen receptors)?

I-CAR T-Cell therapy iwuhlobo lwe-immunotherapy olusebenzisa ama-T-cell alungiswe ngokukhethekile ayingxenye yamasosha ethu omzimba ukulwa nomdlavuza. Isampula yeziguli T amaseli aqoqwa egazini, bese iguqulwa ukuze ikhiqize izakhiwo ezikhethekile ezibizwa nge-chimeric antigen receptors (CAR) ebusweni bazo. Lapho la maseli e-CAR ashintshiwe ephinde afakwe esigulini, lawa maseli amasha ahlasela i-antigen ethile futhi abulale amaseli wesimila.

Isebenza kanjani ukwelashwa kwe-CAR T-Cell?

Ukwelashwa kwe-CAR T-cell kuthatha usizo lwamasosha omzimba ukuze ahlasele futhi abulale amangqamuzana omdlavuza. Lokhu kwenziwa ngokukhipha amangqamuzana athile ashiwo egazini lesiguli, siwalungise elebhu futhi aphinde awajove esigulini. I-CAR T-cell therapy ikhiqize imiphumela ekhuthazayo kakhulu I-non-Hodgkin lymphoma futhi ngaleyo ndlela kuvunywe yi-FDA.

Obani abafanele ukwelashwa kwe-CAR T-Cell?

Njengamanje i-FDA igunyaze ukwelashwa kwe-CAR T-Cell kwezinye izinhlobo ze-Non-Hodgkin lymphoma enamandla futhi ephikisayo futhi ebuyela emuva futhi ephikisayo. i-leukemia enamandla ye-lymphoblastic. Isiguli sidinga ukuthumela imibiko yezokwelapha ephelele ukuze siqinisekise ukusetshenziswa kokwelashwa kwe-CAR T-Cell ekwelapheni kwaso.

Indlela yokufakwa yokwelashwa kwe-CAR T-cell:

1. Iziguli ezine-CD19 + B-cell Lymphoma (Okungenani ama-regimens we-2 chemotherapy ngaphambi kokuhlanganiswa)

2.Ukuba neminyaka eyi-3 kuye kwengama-75

3. Isilinganiso se-ECOG ≤2

4. Abesifazane abanamandla okuthola izingane kumele bathathwe ukuhlolwa komchamo wokukhulelwa futhi kutholakale ukuthi abanalo ngaphambi kokwelapha. Zonke iziguli ziyavuma ukusebenzisa izindlela ezithembekile zokuvimbela inzalo ngesikhathi sesilingo kuze kube kulandelwa okokugcina.

Izindlela zokukhishwa zokwelashwa kwe-CAR T-cell:

1.Ukuphakama komfutho wegazi ophakeme noma ukuquleka

2. Ukwehluleka kokuphefumula

3. Kusatshalaliswe i-coagulation ye-intravascular

4. I-Hematosepsis noma ukutheleleka okusebenzayo okungalawulwa

5. Isifo sikashukela esingalawuleki

Izinzuzo zokwelashwa kwe-CAR T-Cell

1. > Amacala angama-5000 CAR T enziwe ngudokotela onamakhono kakhulu.
2. Izibhedlela eChina zenze izinhlobo eziningi zama-CAR T Cell kufaka phakathi i-CD19 & CD 22 kunanoma yiliphi elinye izwe emhlabeni.
3. I-China iqhuba izivivinyo zomtholampilo ezingaphezu kwama-300 ekwelashweni kwe-CAR T Cell. Ngaphezu kwanoma yiliphi elinye izwe emhlabeni.
4. Umphumela womtholampilo we-CAR T Cell uyefana nalowo wase-USA noma elinye izwe futhi kwesinye isikhathi ungcono.

Inqubo yokwelashwa yokwelashwa kwe-CAR T-Cell

• Qedela ukuhlolwa kwesiguli
• Iqoqo le-T-cell emzimbeni
• Ama-T-cell abese enziwa elebhu
• Ama-T-Cell akhiqizwe ngofuzo abese ephindaphindwa ngokuwasebenzisa akhule elabhorethri. Lawa maseli afriziwe abese ethunyelwa ezikhungweni zokwelashwa.
• Ngaphambi kokufaka, isiguli singanikezwa i-chemotherapy ngomdlavuza waso. Lokhu kusiza ukwelashwa kusebenze ngendlela engcono.
• Kungekudala ngemuva kokulashwa ngamakhemikhali i-CAR T-Cells ifakwa inqubo efana nokufakwa kwegazi.
• Kukhona inyanga yesi-2-3 yesikhathi sokululama kwesiguli.

Isikhathi esibekiwe sokwelashwa kwe-CAR T-Cell

1. Ukuhlolwa nokuhlolwa: isonto elilodwa

2. Pre-treatment & T-Cell Collection: isonto elilodwa

3. Ukulungiswa kweT-Cell nokubuyiselwa: amasonto amabili-amathathu

4. 1st Ukusebenza ngempumelelo: amasonto amathathu

5. Ukuhlaziywa kwe-2nd Ukusebenza kahle: amasonto amathathu.

Imiphumela emibi yokwelashwa kwe-CAR T-Cell

Imiphumela emibi ejwayelekile yokwelashwa kwe-CAR T-cell ifaka:

• I-Cytokine release syndrome
  Kwezinye izimo, iziguli zingase zibe nezimpawu ezinjengomkhuhlane, imfiva, ukugodola, ikhanda elibuhlungu, isicanucanu, ukuhlanza, ukuxega kwendle, imisipha noma izinhlungu zamalunga. Kungase futhi kubangele umfutho wegazi ophansi, ubunzima bokuphefumula, nokushaya kwenhliziyo okusheshayo. Le miphumela engemihle ibangelwa ukukhululwa kwama-cytokines ngamaseli omzimba ngesikhathi sokwelashwa kwe-CAR T-cell. Lezi zimpawu zivame ukuba mnene, kodwa zingaba zimbi futhi zibe sengozini kwezinye iziguli.
• Imicimbi yezinzwa
  Imicimbi ye-neurological ingenzeka futhi ingaba yimbi kwezinye iziguli. Imicimbi enjalo ifaka i-encephalopathy (ukulimala kwengqondo nokungasebenzi kahle), ukudideka, ukukhuluma kanzima, ukukhathazeka, ukuquleka, ukozela, ukushintsha kwesimo sokwazi nokulahlekelwa ibhalansi.
• I-Neutropaenia ne-Anemia
  Ezinye iziguli zingase zibe ne-neutropenia noma isibalo esiphansi samaseli amhlophe. Ngokufanayo, i-anemia noma isibalo esiphansi samangqamuzana abomvu egazi kungenzeka futhi ngenxa yalokhu kwelashwa.
  .
  Ngenhlanhla, iningi lale miphumela engemihle ivamise ukuzixazulula ngokwayo noma ingaphathwa ngokusetshenziswa kwemithi.

Luphumelela kangakanani ukwelashwa kwe-CAR T-Cell?

I-CAR T-cell therapy yokwelapha i-lymphoma kanye neminye imidlavuza yegazi ibonise imiphumela ethembisayo. Kusukela ekwelashweni kwe-CAR T-cell, iziguli eziningi ezazibuye zabuyela emuva amathumba egazi abe nemiphumela ethembisayo futhi abukho ubufakazi bomdlavuza. Iphinde yasiza ekuhlumelelweni kwezimilo zeziguli ezike zahluleka ngaphambilini ukusabela ekwelashweni komdlavuza wendabuko.

Kodwa-ke, izifundo zesikhathi eside zesibalo esikhulu sesiguli ziyadingeka ukuqinisekisa ukusebenza kwalokhu kwelashwa. Ukuhlolwa okukhulu kuzosiza ekutholeni amathuba okuba nemiphumela engemihle nezindlela ezifanele zokubhekana nayo.

Kubiza malini ukwelashwa kwe-CAR T-Cell?

I-China ingumholi womhlaba we-CAR-T cell therapy & BMT. Kuze kube manje kunezinhlolo zomtholampilo zamaseli e-CAR-T ezingaphezu kuka-300 eziqhubekayo. Ukwelashwa kwe-CAR-T yaseShayina kuyisabelomali esikhulu kunazo zonke emhlabeni. Ngoba ukulungiswa kweseli ye-CAR-T kumahhala manje! Iziguli kufanele zikhokhele kuphela ukwelashwa nezinkonzo. Izindleko zokwelashwa zizoba cishe ku-$60,000-$80,000.

Funda nalokhu: Ukwelashwa kwe-CAR T Cell eNdiya 

Ngingayithatha kanjani i-CAR T-Cell therapy e-China?

Isiguli singashayela ku- +91 96 1588 1588 noma i-imeyili ku-cancerfax@gmail.com nemininingwane yesiguli nemibiko yezokwelapha futhi sizohlela umbono wesibili, uhlelo lokwelashwa kanye nesilinganiso sezindleko.